Environmental Enrichment and Social Isolation Mediate Neuroplasticity of Medium Spiny Neurons through the GSK3 Pathway.

Autor:	Scala F; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Biophysics Graduate Program, Institute of Human Physiology, Università Cattolica, Rome, Italy., Nenov MN; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA., Crofton EJ; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Neuroscience Graduate Program, The University of Texas Medical Branch, Galveston, TX 77550, USA., Singh AK; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA., Folorunso O; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA., Zhang Y; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Pharmacology and Toxicology Graduate Program, The University of Texas Medical Branch, Galveston, TX 77550, USA., Chesson BC; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Pharmacology and Toxicology Graduate Program, The University of Texas Medical Branch, Galveston, TX 77550, USA., Wildburger NC; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA., James TF; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Neuroscience Graduate Program, The University of Texas Medical Branch, Galveston, TX 77550, USA., Alshammari MA; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Pharmacology and Toxicology Graduate Program, The University of Texas Medical Branch, Galveston, TX 77550, USA; Studies Abroad Program, King Saud University, Riyadh, Saudi Arabia., Alshammari TK; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Pharmacology and Toxicology Graduate Program, The University of Texas Medical Branch, Galveston, TX 77550, USA; Studies Abroad Program, King Saud University, Riyadh, Saudi Arabia., Elfrink H; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Bench Tutorials Program: Scientific Research and Design, The University of Texas Medical Branch, Galveston, TX 77550, USA., Grassi C; Institute of Human Physiology, Università Cattolica, Rome, Italy; Fondazione Policlinico Universitario A. Gemelli, Rome, Italy., Kasper JM; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Center for Addiction Research, The University of Texas Medical Branch, Galveston, TX 77550, USA., Smith AE; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Center for Addiction Research, The University of Texas Medical Branch, Galveston, TX 77550, USA; Cell Biology Graduate Program, The University of Texas Medical Branch, Galveston, TX 77550, USA., Hommel JD; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Center for Addiction Research, The University of Texas Medical Branch, Galveston, TX 77550, USA., Lichti CF; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX 77550, USA., Rudra JS; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA., D'Ascenzo M; Institute of Human Physiology, Università Cattolica, Rome, Italy., Green TA; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Center for Addiction Research, The University of Texas Medical Branch, Galveston, TX 77550, USA., Laezza F; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77550, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX 77550, USA; Center for Addiction Research, The University of Texas Medical Branch, Galveston, TX 77550, USA. Electronic address: felaezza@utmb.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2018 Apr 10; Vol. 23 (2), pp. 555-567.
DOI:	10.1016/j.celrep.2018.03.062
Abstrakt:	Resilience and vulnerability to neuropsychiatric disorders are linked to molecular changes underlying excitability that are still poorly understood. Here, we identify glycogen-synthase kinase 3β (GSK3β) and voltage-gated Na + channel Nav1.6 as regulators of neuroplasticity induced by environmentally enriched (EC) or isolated (IC) conditions-models for resilience and vulnerability. Transcriptomic studies in the nucleus accumbens from EC and IC rats predicted low levels of GSK3β and SCN8A mRNA as a protective phenotype associated with reduced excitability in medium spiny neurons (MSNs). In vivo genetic manipulations demonstrate that GSK3β and Nav1.6 are molecular determinants of MSN excitability and that silencing of GSK3β prevents maladaptive plasticity of IC MSNs. In vitro studies reveal direct interaction of GSK3β with Nav1.6 and phosphorylation at Nav1.6 T1936 by GSK3β. A GSK3β-Nav1.6 T1936 competing peptide reduces MSNs excitability in IC, but not EC rats. These results identify GSK3β regulation of Nav1.6 as a biosignature of MSNs maladaptive plasticity. (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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